The application of the silicone derivatives in medicine started in the 1930's and since then they have been applied extensively.
As to the group of silicone derivatives, the application of silicone polymers are really widespread in the field of pharmaceutics, because they have several advantageous characteristics, such as high flexibility, heat-resistance, beneficial chemical resistance, they are indifferent to the human organism, they have no interaction with it in the course of pharmaceutical application.
Silicone polymers—polyorganosiloxanes—are polymer compounds, wherein organic chemical groups are attached to the siloxane chains (—Si—O—Si—).
By the hydrolysis or condensation of chlorosilane monomers different silicone polymers can be prepared. These polymers have three main groups depending on their structures:                silicone oils and natural elastomers with linear structure,        silicone resins with branched structure,        silicone resins with cross-linked structure (most of the silicone resins have cross-linked structure).        
Not only silicone oils with different degree of viscosity but also fat silicones, antifoams, form release agents and hydrophobizing agents can be prepared from the silicone polymers. Silicone rubbers are prepared from silicon caoutchoucs by different vulcanizing and cross-linking processes.
Resins can be used as pressing powders, pressing resins, resin emulsions, lacquers (solutions with different solvents) and pigmented paints or resins modified with organic components.
Silicone polymers are important basic materials of the pressure sensitive adhesives (PSA), medicinal and surgical implants, prostheses used in the therapy and different transdermal therapeutic systems (TTS).
Among the silicone oils dimethyl polysiloxanes are applied most often in the therapy. These silicone oils have very strong antifoaming properties, which arise from their low surface tension (approximately 20 mN/m, for comparison the surface tension of water is 85 mN/m). This advantage is employed by the application of silicone oil in sprays for the treatment of lung oedema. In case of lung oedema the strongly foamy mucus originating from the lung and malting a barrier in the normal ventilation and in the oxygen uptake can cause anoxia or suffocation in lack of treatment. The hydrophobic characteristics of silicone oils are used in pharmaceutical preparations for the treatment of bedsore and ulcer with patients who have to stay in a single decubitus position for a lengthy period.
One sub-group of silicone oils are the highly volatile silicones. The highly volatile silicones are pharmaceutical carriers which are able to evaporate completely from the surface of the human skin within 6 hours. The pharmaceutical use of these carriers has not been exhausted every possibility, yet.
The subject of the present invention is a pharmaceutical transdermal preparation, wherein the particles of the active ingredient are coated with hexamethyldisiloxane, octamethyltrisiloxane and decamethylpentacyclosiloxane. These highly volatile silicone oils are widely used in the cosmetics industry and their pharmaceutical application is also known.
U.S. Pat. Nos. 4,355,046 and 5,336,692 describe the use of hexamethyldisiloxane, octamethyltrisiloxane and decamethylpentacyclosiloxane solvents in ointments having a petrolatum base. The ointments are applied in cosmetics and medicine. According to these patents highly volatile siloxanes serve exclusively in order to obtain a good distribution on the surface of the human skin, but not to attain chemical and microbiological stability. The type and the composition of the pharmaceutical preparations and also the ointment base cited in the descriptions are different from the subject of the present invention. In U.S. Pat. No. 5,210,103 hexamethyldisiloxane is used as power gas in skin foams for external use (for example: vaginal).
European Patent No. EP 914082 relates to an antiperspirant composition containing volatile siloxanes. These silicones assure the suitable consistency of the composition and avoid any leakage of the product from the packaging.
By the production of Diprolene Creme® (Schering Plough) and Dexeryl Creme® (Pierre Fabre Sante) decamethylpentacyclosiloxane is used to assure the aesthetics of the product.
All of the above cited documents describe cosmetic compositions wherein the volatile siloxanes are used to assure the suitable consistency of the compositions and the aesthetics of the products.
Volatile siloxanes are rarely applied in pharmaceutical compositions as ingredients. The composition of the pharmaceutical preparations cited in the literature are different from the subject of the present invention, and in the pharmaceutical compositions of the state of the art, similarly to the cosmetic products, volatile siloxanes serve to obtain a good distribution on the surface of the skin.
At the same time in the present invention volatile silicone oils assure chemical and microbiological stability and good bioavailability to our composition.
The basic requirements of pharmaceutical ointments and creams containing an active ingredient are good stability, long storage time, suitable penetration of the active substance from the transdermal system, good consistency and easy application to the skin.
A disadvantage of the ointments having fatty or oily bases is that the penetration of the active ingredient is slow and the amount of the released active substance is low, because in the lipophil phase the solubility of the ointment is higher, especially in case of active substances having low aqueous solubility, and therefore, the distribution is not equal, the ointment base contains more active substance. Examples of active ingredients with low aqueous solubility are aciclovir, piroxicam, meloxicam, ibuprofen, diclofenac sodium and potassium salt, clotrimazol, bifonazol, metronidazol, nifedipin, nitroglycerin and cetirizin. Examples for creams containing the above active ingredients are Zovirax® (aciclovir), Feldene® (piroxicam), Hotemin® cream (piroxicam), Canesten® cream (clotrimazol), Mycospor® cream (bifonazol) or Rozex® cream (metranidazol).
Gel compositions containing the active ingredient in a suspended form are known from the literature, wherein the release of the active substance is adequate, but stability problems can occur during storage. These problems are caused by the chemical and microbiological reactions on the contact areas of the different surfaces, which may change the chemical condition of the active substance. These kind of stability problems can occur for example during the storage of Hotemin® cream containing piroxicam, Voltaren® emulgel (diclofenac) or Rozex® gel containing metronidazol.